Evaluation of single agents and combinations of chemotherapeutic agents in mouse colon carcinomas

Abstract

Single agents and combinations of agents were tested for antitumor activity against four transplantable colon tumors in mice. The most impressive anti-tumor activity was obtained with anguidine and the combination of anguidine + 5-FU against colon adenocarcinoma No. 38. Antitumor potentiation was obtained when the combination was injected simultaneously on a Q7d schedule (two experiments), but not on an alternating schedule of administration (3 or 4 days separating injections of the two agents). Anguidine was highly active only in a colon tumor that was very responsive to 5-FU. The correlation between high 5-FU sensitivity and high anguidine sensitivity may be coincidental or could be of predictive value. Other active single agents and combinations of agents against one or more of the colon tumors include 5-FU, 5-FUdR, MeCCNU, BCNU, homoharringtonine, ara-C, Cis-Pt-II, dianhydrogalactitol, piperazinedione, cyclophosphamide; MeCCNU + 5-FU; Adriamycin + 5-FU; Adriamycin + cyclophosphamide; Adriamycin + palmO-ara-C; cyclophosphamide + procarbazine; and 5-FU + palmO-ara-C. (The combination of 5-FU + palmO-ara-C was potentiating only on an alternating schedule.) The results of surgery-chemotherapy adjuvant treatment of metastatic colon tumors established that if an agent or a combination was highly active against moderately advanced tumor masses, this treatment was also highly active after surgery against residual metastatic disease. The converse was also true. That is, if the agent or combination was inactive or marginally active against moderately advanced disease, the treatment was also relatively ineffectual after surgery against residual metastatic disease. Based on surgical-adjuvant experiments with colon tumor No. 26, the following agents and combinations are conditionally recommended: MeCCNU + 5-FU; MeCCNU + Ara-C; cyclophosphamide + Ara-C; BCNU+ 5-FU and MeCCNU. It is also assumed that those agents active against the advanced disease are likely to be active after surgery against residual metastatic cells. Thus, agents highly active against advanced-stage colon adenocarcinoma No. 38 are possible candidates for adjuvant therapy. On this basis, anguidine and anguidine + 5-FU are recommended.